Addressing infectious disease in a therapeutically relevant fashion requires an understanding of both the microbial virulence factors that contribute to the disease process and how these factors impact the host immunological and inflammatory response to define the clinical outcome. Achieving this understanding provides a perfect opportunity for clinically relevant translational research and is the overriding theme of our proposed Center for Microbial Pathogenesis and Host Inflammatory Responses. The key element in the development of our Center is to bring together promising young investigators, each under the mentorship of established senior faculty, whose research is consistent with this scientific theme. The underlying hypothesis that ties these investigators together is that targeting diverse pathogens and pathogenic processes in an integrated, highly structured environment will optimize opportunities for the elucidation of common themes with respect to the host response and its adverse consequences on the disease process. To this end, this application brings together as Project Leaders junior investigators who focus on viral (Forrest), bacterial (Scurlock), and parasitic (Stumhofer) pathogens. Additionally, based on studies suggesting that persistent viral and bacterial infection plays a key role in the development of many chronic diseases, a fourth investigator (Ortmann) will focus on the host response in inflammatory arthritis, the principal example of which is rheumatoid arthritis. We propose to (Aim 1) enact an integrated and interactive faculty development plan for young investigators in the context of the underlying scientific theme with the immediate goal of leveraging the resources of the Center to enable these investigators to establish independent research careers and taking specific steps to ensure the absence of administrative or technical barriers to their success; (Aim 2) strengthen the biomedical research infrastructure on the host campuses of the University of Arkansas for Medical Sciences and Arkansas Children's Hospital; and (Aim 3) build on the success of these first two aims to recruit additional junior faculty and create the collaborative and synergistic environment required to establish a self-sustaining Center of Biomedical Research Excellence. As a means of further optimizing the academic, experimental, and translational synergy, specific consideration is also given to integration with existing NCRRfunded programs on the host campuses. These include the Arkansas INBRE, the UAMS CTSA Center for Clinical and Translational Research, and the Center for Translational Neuroscience, an established COBRE. Bringing all of these elements together will provide an integrated and supportive research infrastructure that will significantly enhance the ability of th Project Leaders to establish independent, extramurally funded research programs. The long-term goal is to integrate the Project Leaders included in this application with newly recruited junior investigators and with established investigators who can significantly expand their existing research programs in a manner consistent with the underlying scientific theme, to create the collaborative and translational synergy required for the development of successful program project applications and a self-sustaining translational research center that can impact human health.